A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.

Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94R⊕ to 2.85R⊕. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.

A dense ring of the trans-Neptunian object Quaoar outside its Roche limit.

Planetary rings are observed not only around giant planets1, but also around small bodies such as the Centaur Chariklo2 and the dwarf planet Haumea3. Up to now, all known dense rings were located close enough to their parent bodies, being inside the Roche limit, where tidal forces prevent material with reasonable densities from aggregating into a satellite. Here we report observations of an inhomogeneous ring around the trans-Neptunian body (50000) Quaoar. This trans-Neptunian object has an estimated radius4 of 555 km and possesses a roughly 80-km satellite5 (Weywot) that orbits at 24 Quaoar radii6,7. The detected ring orbits at 7.4 radii from the central body, which is well outside Quaoar's classical Roche limit, thus indicating that this limit does not always determine where ring material can survive. Our local collisional simulations show that elastic collisions, based on laboratory experiments8, can maintain a ring far away from the body. Moreover, Quaoar's ring orbits close to the 1/3 spin-orbit resonance9 with Quaoar, a property shared by Chariklo's2,10,11 and Haumea's3 rings, suggesting that this resonance plays a key role in ring confinement for small bodies.

Treating Brain Metastases from Breast Cancer: Outcomes after Stereotactic Radiosurgery.

AIMS: Stereotactic radiosurgery (SRS) is an alternative to surgery or whole brain radiotherapy for the control of single or multiple brain metastases in patients with breast cancer. To date, there is no clear consensus on factors that might predict overall survival following SRS. The aim of this study was to assess the overall survival of breast cancer patients with brain metastases treated with SRS at a single centre and to examine the factors that might influence survival. MATERIALS AND METHODS: A retrospective analysis of consecutive patients with breast cancer and brain metastases, considered suitable for SRS by the regional neuro-oncology multidisciplinary team. All patients were treated at a single National Health Service centre. RESULTS: In total, 91 patients received SRS between 2013 and 2017, of whom 15 (16.5%) were alive at the time of analysis. The median overall survival post-SRS was 15.7 months (interquartile range 7.7-23.8 months) with no significant effect of age on survival (67 patients ≤ 65 years, 16.3 months; 26 patients > 65 years, 11.4 months, P = 0.129). The primary tumour receptor status was an important determinant of outcome: 31 oestrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) patients had a median overall survival of 13.8 months, 14 ER+/HER2+ patients had a median overall survival of 21.4 months, 30 ER-/HER2+ patients had a median overall survival of 20.4 months and 16 patients with triple negative breast cancer (TNBC) had a median overall survival of 8.5 months. A larger total volume of tumour treated (>10 cm3), but not the number of individual metastases treated, was associated with worse survival (P = 0.0002) in this series. Patients with stable extracranial disease at the time of SRS had improved overall survival compared with those with progressive extracranial disease (30 patients stable extracranial disease overall survival = 20.1 months versus 33 patients progressive extracranial disease overall survival = 11.4 months; P = 0.0011). Seventeen patients had no extracranial disease at the time of SRS, with a median overall survival of 13.1 months. CONCLUSIONS: This single-centre series of consecutive patients with brain metastases from breast cancer, treated with SRS, had a similar overall survival compared with previous studies of SRS. TNBC and ER+/HER2- histology, metastatic volumes >10 cm3 and progressive extracranial disease at the time of SRS were associated with worse survival.

An extremely rare case of a high-grade pleomorphic cardiac sarcoma and likely cerebral metastasis in a young patient.

To date, there have been less than a 100 confirmed case reports of primary cardiac malignant fibrous histiocytomas, a rare form of sarcoma. In this report, we discuss the case of a 15-year-old girl who initially presented with a histiocytic cerebral sarcoma that was treated with aggressive resection and chemotherapy. Three years later, the same patient developed increasing shortness of breath and was found to have a high-grade pleomorphic undifferentiated cardiac sarcoma that likely represents the primary tumour from which the cerebral lesion metastasised. This represents an extremely unique case; in 2010, a research group in Germany claimed the very first description of a true cardiac sarcoma with brain metastasis [1]. However, even as far back as 1960, there were three case reports [2] and more extensive sarcoma studies recently have revealed further cases [3]. Nevertheless, there have probably been less than 10 cases in the literature up until this point.

Tapered Implants in Dentistry: Revitalizing Concepts with Technology: A Review.

The most common approach to lessen treatment times is by decreasing the healing period during which osseointegration is established. Implant design parameters such as implant surface, primary stability, thread configuration, body shape, and the type of bone have to be considered to obtain this objective. The relationship that exists between these components will define the initial stability of the implant. It is believed implant sites using a tapered design and surface modification can increase the primary stability in low-density bone. Furthermore, recent experimental preclinical work has shown the possibility of attaining primary stability of immediately loaded, tapered dental implants without compromising healing and rapid bone formation while minimizing the implant stability loss at compression sites. This may be of singular importance with immediate/early functional loading of single implants placed in poor-quality bone. The selection of an implant that will provide adequate stability in bone of poor quality is important. A tapered-screw implant design will provide adequate stability because it creates pressure on cortical bone in areas of reduced bone quality. Building on the success of traditional tapered implant therapy, newer tapered implant designs should aim to maximize the clinical outcome by implementing new technologies with adapted clinical workflows.

Robotic-assisted laparoscopic radical cystoprostatectomy and extracorporeal continent urinary diversion: highlight of surgical techniques and outcomes.

BACKGROUND: We report our technique for robotic-assisted laparoscopic radical cystoprostatectomy (RARCP) and extracorporeal urinary diversion and present their clinical outcomes. METHODS: Between October 2003 and December 2008 we performed 58 RARCPs with extracorporeal continent urinary diversion. Preoperative, operative and postoperative data was evaluated. RESULTS: Mean patient age was 68 (range 46-89) years, with an average American Society of Anesthesiologists classification of 2.9. Mean operative time was 8 (range 5-11) h. Median blood loss was 450 ml. Thirteen patients received intra-operative blood transfusions and 22 patients received peri-operative blood transfusions. Continent urinary diversions were performed by means of the Studer technique (n = 42) or Indiana pouch (n = 16). Mean number of lymph nodes examined on lymphadenectomy was 27 (range 0-52). CONCLUSIONS: Our RARCP and continent diversion technique is a safe and feasible option for primary urothelial carcinoma of the bladder. Oncological and surgical outcomes are comparable to open cystectomy series.

A single p450 allele associated with insecticide resistance in Drosophila.

Insecticide resistance is one of the most widespread genetic changes caused by human activity, but we still understand little about the origins and spread of resistant alleles in global populations of insects. Here, via microarray analysis of all P450s in Drosophila melanogaster, we show that DDT-R, a gene conferring resistance to DDT, is associated with overtranscription of a single cytochrome P450 gene, Cyp6g1. Transgenic analysis of Cyp6g1 shows that overtranscription of this gene alone is both necessary and sufficient for resistance. Resistance and up-regulation in Drosophila populations are associated with a single Cyp6g1 allele that has spread globally. This allele is characterized by the insertion of an Accord transposable element into the 5' end of the Cyp6g1 gene.

Periodontal considerations in restorative and implant therapy.

The successful integration of periodontal and restorative dentistry for both natural teeth and implants requires knowledge and application of both mechanical and biological principles. In areas of aesthetic concern, an adequate band of attached gingiva can increase patient comfort, reduce the probability of gingival recession following tooth preparation and simplify restorative procedures. While some restorative margins need to be placed at or below the margin of the free gingiva, this should be considered to be a compromise, and margins should not be placed more than 0.5 mm into a healthy gingival sulcus. Approximately 2-3 mm of healthy, natural supra-alveolar tooth surface is needed for attachment of the gingival tissues to the tooth. This dimension is called the biological width. If adequate biological width does not exist, surgical or orthodontic procedures to expose healthy tooth structure are recommended before final restorations are placed. Retraction of soft tissues for impressions is best accomplished with mechanical methods rather than lasers or electrosurgery because of the potentially harmful effects of these devices to the cementum, bone and soft tissues surrounding the teeth. Implants function best and withstand occlusal forces optimally when loaded in a vertical direction. Therefore, planning implant placement is critical for success. Because of increased proprioception, it is suggested that natural teeth be used to guide the occlusion in partially edentulous patients. Cantilevers should be used with caution and with appropriate attention to occlusal forces. While occlusal trauma does not cause periodontal disease, it may contribute to bone loss around teeth and implants. In the opinion of the authors, provisional restorations are an integral part of dental and periodontal therapy. They can be used to establish aesthetic and physiological contours that can be easily cleaned by patients and they can also be used as a guide for any needed surgical tissue modification.

Resistance of Drosophila to toxins.

Insects, including Drosophila, readily respond to toxins such as phytotoxins, metal ions, and insecticides in their environment by evolving resistance. Although Drosophila are seldom targets for insecticides, nevertheless populations worldwide have evolved resistance to a variety of insecticides, and these resistance alleles persist in high frequency. In many cases, Drosophila use the same genetic and biochemical mechanisms that underlie resistance in pest insects, including single-site changes in target molecules resulting from point mutations and upregulation of degradative enzymes, particularly cytochrome P450 enzymes and glutathione S-transferases. However, several types of resistance found in pest insects, such as gene amplification and knock-down resistance, have not been reported in Drosophila field populations. Excellent Drosophila-plant models are being studied to understand the adaptation to phytotoxins; P450 enzymes are clearly involved in phytotoxin resistance in one of these models. The genetic advantages of D. melanogaster, including availability of the sequenced genome, should allow further study of these genes and identification of new ones, particularly regulatory genes, responsible for resistance.

Asymptomatic renal neoplasms in the rectal cancer patient.

Although cancers of the rectum and kidney are common malignancies the incidence of coexistent rectal and renal primary tumors is unclear. Our objective was to determine the true incidence of synchronous neoplasms of the rectum and kidney. The computed tumor registry database at the City of Hope National Medical Center was queried for patients with synchronous rectal cancer and renal neoplasms presenting between August 1990 and August 2000. During the 10-year period there were 182 patients presenting for treatment of rectal carcinoma. Of these seven (3.8%) were found to have an asymptomatic renal neoplasm. Four patients underwent synchronous resection. Three patients underwent staged renal and rectal resections. The pathology of the renal lesions included renal cell carcinoma in six and an oncocytoma in one patient. Rectal lesions were all adenocarcinomas and all were within 10 cm of the dentate line. Three patients required abdominoperineal resections and four were treated with low anterior resections. Two patients presented with hepatic metastasis at the time of diagnosis. Five patients remain free of disease. Two patients died of persistent and recurrent disease 6 months and 40 months after operation. With the exception of one patient who required prolonged intubation because of severe Parkinson's disease there were no major complications after simultaneous resection of both renal and rectal disease. Simultaneous asymptomatic renal neoplasms may be found in up to 3.8 per cent of patients with rectal cancer. Synchronous lesions may be treated simultaneously without significant morbidity.

Stress-reactivity and juvenile hormone degradation in Drosophila melanogaster strains having stress-related mutations.

Juvenile hormone (JH) degradation was studied under normal and stress conditions in young and matured females of Drosophila melanogaster strains having mutations in different genes involved in responses to stress It was shown that (1) the impairment in heat shock response elicits an alteration in stress-reactivity of the JH system; (2) the impairment JH reception causes a decrease of JH-hydrolysing activity and of stress-reactivity in young females, while in mature ones stress reactivity is completely absent; (3) the absence of octopamine results in higher JH-hydrolysis level under normal conditions and altered JH stress-reactivity; (4) the higher dopamine content elicits a dramatic decrease of JH degradation under normal conditions and of JH stress-reactivity. Thus, the impairments in any component of the Drosophila stress reaction result in changes in the reponse of JH degradation system to stress. The role of JH in the development of the insect stress reaction is discussed.

Intracellular localization and tissue specificity of the Methoprene-tolerant (Met) gene product in Drosophila melanogaster.

The Methoprene-tolerant (Met) gene product in Drosophila melanogaster facilitates the action of juvenile hormone (JH) and JH analog insecticides. Previous work resulted in the cloning and identification of the gene as a member of the bHLH-PAS family of transcriptional regulators. A Met(+) cDNA was expressed in Escherichia coli, and polyclonal antibody was prepared against the purified protein. A single band on a Western blot at the expected size of 79kD was detected in extracts from Met(+) larvae but not from Met(27) null mutant larvae, demonstrating the antibody specificity. Antibody detected MET in all stages of D. melanogaster development and showed tissue specificity of its expression. MET is present in all cells of early embryos but dissipates during gastrulation. In larvae it is present in larval fat body, certain imaginal cells, and immature salivary glands. In pupae it persists in fat body cells and imaginal cells, including abdominal histoblast cells. In adult females MET is present in ovarian follicle cells and spermathecae; in adult males it is present in male accessory gland and ejaculatory duct cells. In all of these tissues MET is found exclusively in the nucleus. Some of these tissues are known JH target tissues but others are not, suggesting either the presence of novel JH target tissues or another function for MET.

Chemical and gamma-ray mutagenesis of the white gene in Aedes aegypti.

A molecular understanding of an insect gene can be facilitated by analysing the phenotypes of mutants for that gene. Protocols were developed for both chemical and gamma-ray mutagenesis in Aedes aegypti using the white (w) gene as an assay. Wild-type adult males were subjected to varying doses of either ethyl methanesulphonate (0. 1%, 0.5% or 1%) or gamma rays (1500 R or 3000 R), mated to females homozygous for the recessive w mutation, and progeny screened for the w phenotype, indicating non-complementation. The expression of newly induced w alleles was either complete or mosaic. Gamma-ray mutagenesis resulted in high (1.65 or 6.39%, depending on dose) induction of mutant alleles for the w gene, but not for a different gene, red-eye (0.15%). Gamma-ray-induced w alleles did not revert at a reasonable frequency following additional irradiation, suggesting that the high rate of gamma-ray-induced w mutagenesis is not due to a transposon insertion event.

Biological complications with dental implants: their prevention, diagnosis and treatment.

Biofilms form on all hard non-shedding surfaces in a fluid system, i.e. both on teeth and oral implants. As a result of the bacterial challenge, the host responds by mounting a defence mechanism leading to inflammation of the soft tissues. In the dento-gingival unit, this results in the well-described lesion of gingivitis. In the implanto-mucosal unit, this inflammation is termed "mucositis". If plaque is allowed to accumulate for prolonged periods of time, experimental research has demonstrated that "mucositis" may develop into "periimplantitis" affecting the periimplant supporting bone circumferentially. Although the bony support may be lost coronally, the implant still remains osseointegrated and hence, clinically stable. This is the reason why mobility represents an insensitive, but specific diagnostic feature of "periimplantitis". More sensitive and more reliable parameters of developing and existing periimplant infections are "bleeding on probing", "probing depths" and radiographic interpretation of conventional or subtraction radiographs. Depending on the diagnosis made continuously during recall visits, a maintenance system termed Cumulative Interceptive Supportive Therapy (CIST) has been proposed.

NCCN Practice Guidelines for Prostate Cancer.

Systemic therapies for prostate cancer are likely to improve, and as they do, they will have enormous impact on the treatment of high-risk and locally advanced cancers. Further technical improvements in radiotherapy and alternative local modalities, such as cryoablation, are also likely, and will bring even more options for local control. It is certain these guidelines will continue to evolve.

Stress-reactivity of a Drosophila melanogaster strain with impaired juvenile hormone action.

Met(27) is a null allele of the Methoprene-tolerant gene of D. melanogaster that shows resistance to the toxic effects of both juvenile hormone (JH) and a JH analog, methoprene. The mechanism of resistance appears to be altered JH reception. We measured fertility, JH-hydrolyzing activity, and dopamine (DA) levels in Met(27) and Met(+) flies under normal (25 degrees C) and heat-stress (38 degrees C) conditions. We show that under normal conditions Met(27) females have JH-hydrolyzing activity and fertility lower than Met(+), but DA content did not differ between the two strains. At 38 degrees C Met(27) flies show no impairment in JH-hydrolyzing activity in response to stress, but they do show lower DA levels and impaired reproduction. The results with Met(27) are consistent with the previous hypothesis that the alteration in fertility that follows heat stress in D. melanogaster could result from alteration in the JH endocrine system.

Simplified technique with short and long-term followup of conversion of an ileal conduit to an Indiana pouch.

PURPOSE: We report a simplified technique for converting an existing conduit to an Indiana pouch as well as short and long-term results. MATERIALS AND METHODS: From May 1988 to February 1998 we evaluated short and long-term outcome and complications in 23 patients 14 to 82 years old (average age 51.8) who underwent conversion of a conduit to an Indiana pouch. When no obstruction of the existing ureteroileal anastomoses was identified, the conduit was freed from the abdominal wall and surrounding bowel. The proximal conduit and ureteral anastomoses were not dissected. The conduit was opened along the antimesenteric wall proximal to the ureteral anastomoses and attached to 25 to 28 cm. of detubularized right colon as a refluxing Studer limb. The pouch was completed in the usual fashion and the stoma was matured at a virgin site. RESULTS: Surgical indications included stomal complications in 10 patients, an infected nonfunctioning kidney in 2 and patient preference in 11. There were no perioperative deaths although 3 patients died of cancer progression. Average operative time was 6.6 hours, estimated blood loss 518 cc and length of stay 7.8 days. Average followup after conversion was 4.7 years (range 0.2 to 11.0). Six late complications developed in 4 cases, including pyelonephritis in 2, severe pouchitis in 1, dehydration in 1 and stomal revision in 2. Renal function was well preserved with an average preoperative and postoperative creatinine of 0.91 and 1.14 mg./dl., respectively. CONCLUSIONS: This technique simplifies conversion and decreases bowel requirements. The low complication rate and stable serum creatinine support the finding that conversion of a conduit to an Indiana pouch is a safe, viable procedure.